MANAGEMENT DECISIONS ON FARM-LEVEL AND THEIR LINK TO WEATHER REQUIREMENTS: A CASE STUDY FOR THE UPPER DANUBE RIVER BASIN

It is undeniable that the global warming has already affected the Earth’s biota, whereby the rise of air temperature is an important factor. Agricultural systems are also affected by climate change via the interrelated biophysical layers. Climate influences farmers` decisions in crop management. To simulate the interactions between climate/weather and the different crop management activities an agent based modelling approach is used, in which farmers` decision making is based on crop requirements from literature. To validate these decision algorithms on how farmers arrange their daily crop management decisions like planting, fertilizing, and harvesting due to changes of climate parameters, a statistical analysis of empirical data (1970-2003) on temperature and different crop growth stages, which represent different management activities, was carried out. Results show that every crop has to be considered separately and the requirements of the different crops on temperature have to be observed in different ways. There are crops which have a low germination temperature, for those the average daily temperature shows no relation with the planting day. In this case the temperature sum in a specific period is more precise. On the opposite side crops with a high germination temperature show significant correlation results with the average daily temperature of a period before the planting day.Crop management, heuristic decisions, regional climate change, Crop Production/Industries, Farm Management,

Efficiency Analysis of East European Electricity Distribution in Transition: Legacy of the Past?

This paper provides a cross-country efficiency analysis of electricity distribution companies in East European transition countries (Poland, Czech Republic, Slovakia and Hungary). We compare the relative technical efficiency of East European regional distribution companies (RDCs) among themselves, as well as with German RDCs. We use the nonparametric DEA, and also apply bootstrapping techniques and the FDH-estimator; in addition, we carry out parametric analyses, mainly SFA (stochastic frontier analysis) and COLS (corrected ordinary least squares). The results suggest that the Polish distribution companies are still inefficiently small. The Czech Republic and Slovakia feature the highest efficiency.Efficiency analysis, Econometric methods, Electricity distribution, Transition, Eastern Europe

Le impeachment américaine et son influence sur la mise en accusation du Chili

This article deals with the origin of the American impeachment, and the manner in which it influenced over the regulation of the Chilean Impeachment, especially regarding aspects such as the authorities that should lead the impeachment; the causes under which an officer may be impeached; and the extent of the sanction affecting the convicted officer.Este artículo trata acerca del origen del impeachment estadounidense y la manera en que este influyó sobre la regulación de la acusación constitucional en Chile, particularmente en aspectos como la elección de los órganos que intervienen en él, las causales por las cuales una autoridad puede ser acusada y el alcance de la sanción que afecta a la autoridad.Cet article concerne le impeachment américain ainsi que son influence à l’égard de la régulation de la acusación constitucional au Chili, notamment en ce qui concerne l’élection des organes impliqués, les motifs par lesquels une autorité peut être accusée et l’étendue de la peine qui peut l’affecter

Generation and characterization of CD19 CAR T cells with PD-1_CD28 fusion receptor

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. 80 to 90% of the children with standard risk can be cured with chemotherapy and stem cell transplantation. Nevertheless, the prognosis for primary refractory or relapsed ALL is still dismal. As a promising treatment strategy for B-ALL, adoptive T-cell transfer of CD19 targeting T cells with chimeric antigen receptor (CAR) has emerged. Clinical studies show remission rates of heavily pretreated patients of up to 90% upon CAR T-cell infusion. Despite temporary remission, around 50% of patients treated with a conventional anti-CD19 CAR suffer from a relapse. Therefore, CAR T-cell treatment needs to be further optimized. Preliminary data of our group suggested that co-inhibitory checkpoint molecules on the surface of leukemic blasts could prevent T cells from sufficient anti-leukemic response. Here, we designed CAR T cells with a fully human PD-1_CD28 checkpoint fusion receptor. This receptor contains an inhibitory extracellular PD-1 and a stimulatory intracellular CD28 domain. Thus, it is able to reverse the inhibitory PD-1/PD-L1 signal of the leukemic cell into a CD28-based stimulatory signal for the T cell. In this study, we successfully generated first and second generation CAR T cells with and without PD-1_CD28 fusion receptor by retroviral transduction. CAR T cells showed good expansion/ viability and a favourable central/ effector memory phenotype. Functionality assays revealed strong activation, killing and proliferation capacity of anti-CD19 CAR T cells upon target-cell recognition. In line with previous publications, second generation CAR T cells showed improved cytokine release compared to first generation CAR T cells. PD-L1 expression on the target cells significantly decreased cytokine release of CAR T cells, although the T cells’ co-inhibitory checkpoint profile was not altered. Inclusion of the PD-1_CD28 fusion receptor did not impair the killing capacity of the CAR and induced no unspecific CD19-independent activation. The killing capacity of CAR T cells with and without fusion receptor showed no significant differences. However, in presence of PD-L1, CAR T cells with fusion receptor could outcompete conventional first and second generation CAR T cells in terms of cytokine release. Further in vivo analyses will be performed to validate these findings. CAR T cells with PD-1_CD28 fusion receptor could be a useful tool to improve CAR T-cell functionality for treatment of advanced pediatric leukemia.Die akute lymphatische Leukämie (ALL) ist die häufigste Krebserkrankung bei Kindern. Heutzutage können 80 bis 90% der erkrankten Kinder mit Hilfe von Chemotherapie und Stammzelltransplantation geheilt werden. Die Prognose für primär refraktäre oder mehrfach rezidivierende ALL ist jedoch weiterhin schlecht. Einen vielversprechenden Therapieansatz bei fortgeschrittener B-ALL stellt die Infusion von gegen CD19 gerichteten T-Zellen mit chimärem Antigenrezeptor (CAR) dar. In klinischen Studien konnte gezeigt werden, dass bis zu 90% der größtenteils schwer vorbehandelten Patienten nach CAR-T-Zell-Gabe eine komplette Remission erlangen. Trotz dieser zeitweiligen Remission erleidet jedoch etwa die Hälfte der Patienten, die mit einem konventionellen anti-CD19 CAR behandelt werden, ein Rezidiv der Grunderkrankung. Eine weitere Erforschung und Optimierung des Therapieansatzes mit CAR-T-Zellen ist somit notwendig. Vorarbeiten unserer Arbeitsgruppe legen nahe, dass ko-inhibitorische Immuncheckpointmoleküle auf der Oberfläche von Leukämiezellen eine erfolgreiche T-Zell-Antwort beeinträchtigen können. Daraufhin entwickelten wir CAR-T-Zellen mit einem zusätzlichen PD-1_CD28 Checkpointfusionsrezeptor. Dieser Rezeptor besteht aus einer inhibitorischen extrazellulären PD-1 und einer stimulatorischen intrazellulären CD28 Domäne. Dadurch kann ein ursprünglich inhibitorisches Signal der Leukämiezelle vermittelt über die PD-1/PD-L1-Achse in ein CD28 vermitteltes stimulatorisches Signal für die T-Zelle umgewandelt werden. In diesem Projekt konnten wir CAR-T-Zellen der ersten und zweiten Generation mit und ohne PD-1_CD28 Fusionsrezeptor mittels retroviraler Transduktion erfolgreich herstellen. Die CAR-T-Zellen besaßen eine gute Expansionsfähigkeit, eine hohe Viabilität und den vorteilhaften Phänotyp einer zentralen Gedächtnis- oder Effektor-Gedächtnis-T-Zelle. Die Funktionalitätstests zeigten ein starkes Aktivierungs-, Killing-, und Proliferations-Vermögen der anti-CD19-CAR-T-Zellen nach Erkennung der Zielzellen. Übereinstimmend mit bisherigen Veröffentlichungen setzten Zweit-Generationen-CAR-T-Zellen verglichen zu Erst-Generationen-CAR-T-Zellen höhere Zytokinmengen frei, obwohl das ko-inhibitorische Checkpointprofil der T-Zellen gleich war. Der Fusionsrezeptor beeinträchtigte die Killing-Rate der CAR-T-Zellen nicht und vermittelte keine unspezifische, CD19-unabhängige Aktivierung. Das Killing-Vermögen der CAR-T-Zellen mit und ohne Fusionsrezeptor zeigte keine signifikanten Unterschiede. Gemessen an der Zytokinausschüttung waren die CAR-T-Zellen mit Fusionsrezeptor in Anwesenheit von PD-L1 den konventionellen Erst- und Zweit-Generationen-CAR-T-Zellen überlegen. Weitere Versuche werden in vivo durchgeführt, um diese Ergebnisse validieren zu können. CAR-T-Zellen mit PD-1_CD28 Fusionsrezeptor könnten ein vielversprechendes Verfahren sein, um die CAR-T-Zell-Funktionalität bei Behandlung von fortgeschrittener pädiatrischen Leukämie in einem Patienten-individualisierten Rahmen zu verbessern

Life-history and hormonal control of aggression in black redstarts: blocking testosterone does not decrease territorial aggression, but changes the emphasis of vocal behaviours during simulated territorial intrusions

Introduction: Many studies in behavioural endocrinology attempt to link territorial aggression with testosterone, but the exact relationship between testosterone and territorial behaviour is still unclear and may depend on the ecology of a species. The degree to which testosterone facilitates territorial behaviour is particularly little understood in species that defend territories during breeding and outside the breeding season, when plasma levels of testosterone are low. Here we suggest that species that defend territories in contexts other than reproduction may have lost the direct regulation of territorial behaviour by androgens even during the breeding season. In such species, only those components of breeding territoriality that function simultaneously as sexually selected signals may be under control of sex steroids.<p></p> Results: We investigated black redstarts (Phoenicurus ochruros), a species that shows periods of territoriality within and outside of the breeding season. We treated territorial males with an anti-androgen and an aromatase inhibitor during the breeding season to block both the direct and indirect effects of testosterone. Three and ten days after the treatment, implanted males were challenged with a simulated territorial intrusion. The treatment did not reduce the overall territorial response, but it changed the emphasis of territoriality: experimental males invested more in behaviours addressed directly towards the intruder, whereas placebo-treated males put most effort into their vocal response, a component of territoriality that may be primarily directed towards their mating partner rather than the male opponent.<p></p> Conclusions: In combination with previous findings, these data suggest that overall territoriality may be decoupled from testosterone in male black redstarts. However, high levels of testosterone during breeding may facilitate-context dependent changes in song

Testosterone affects song modulation during simulated territorial intrusions in male black redstarts (Phoenicurus ochruros)

Although it has been suggested that testosterone plays an important role in resource allocation for competitive behavior, details of the interplay between testosterone, territorial aggression and signal plasticity are largely unknown. Therefore, we investigated if testosterone acts specifically on signals that communicate the motivation or ability of individuals to engage in competitive situations in a natural context. We studied the black redstart, a territorial songbird species, during two different life-cycle stages, the early breeding phase in spring and the non-breeding phase in fall. Male territory holders were implanted with the androgen receptor blocker flutamide (Flut) and the aromatase inhibitor letrozole (Let) to inhibit the action of testosterone and its estrogenic metabolites. Controls received a placebo treatment. Three days after implantation birds were challenged with a simulated territorial intrusion (STI). Song was recorded before, during and after the challenge. In spring, both treatment groups increased the number of elements sung in parts of their song in response to the STI. However, Flut/Let-implanted males reacted to the STI with a decreased maximum acoustic frequency of one song part, while placebo-implanted males did not. Instead, placebo-implanted males sang the atonal part of their song with a broader frequency range. Furthermore, placebo-, but not Flut/Let-implanted males, sang shorter songs with shorter pauses between parts in the STIs. During simulated intrusions in fall, when testosterone levels are naturally low in this species, males of both treatment groups sang similar to Flut/Let-implanted males during breeding. The results suggest that song sung during a territorial encounter is of higher competitive value than song sung in an undisturbed situation and may, therefore, convey information about the motivation or quality of the territory holder. We conclude that testosterone facilitates context-dependent changes in song structures that may be honest signals of male quality in black redstarts